Medicament delivery device with cartridge sensor and cartridge holder door sensor and method of controlling the device

ABSTRACT

A medicament delivery device is presented for the administration of one or more drug agents, wherein the device comprises a retainer for holding a medicament cartridge. The retainer is moveable between an open and closed position. A position sensor for generating a position output is indicative of whether the retainer is in the open or closed position. Further, a cartridge sensor generates a cartridge output indicative of whether the retainer is holding a medicament cartridge. A controller controls a predetermined operation of the device in dependence on the output of the position sensor and on the output of the cartridge sensor.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a U.S. National Phase application pursuant to35 U.S.C. §371 of International Application No. PCT/EP2012/059751 filedMay 24, 2012, which claims priority to European Patent Application No.11167533.6 filed May 25, 2011. The entire disclosure contents of theseapplications are herewith incorporated by reference into the presentapplication.

TECHNICAL FIELD

This invention relates to a medicament delivery device, and method ofcontrolling the device, for the administration of one or more drugagents to a patient, and in particular but not exclusively, for theself-administration of the drug agent(s).

BACKGROUND

Certain disease states require treatment using one or more differentmedicaments. Some drug compounds need to be delivered in a specificrelationship with each other in order to deliver the optimum therapeuticdose. Although the present patent application is applicable to singlemedicament devices, it is of benefit where combination therapy isdesirable, but not possible in a single formulation for reasons such as,but not limited to, stability, compromised therapeutic performance andtoxicology.

For example, in some cases it might be beneficial to treat a diabeticwith a long acting insulin (also may be referred to as the first orprimary medicament) along with a glucagon-like peptide-1 such as GLP-1or GLP-1 analog (also may be referred to as the second drug or secondarymedicament).

Accordingly, there exists a need to provide devices for the delivery ofone or more medicament in a single injection or delivery step that issimple for the user to perform without complicated physicalmanipulations of the drug delivery device.

SUMMARY

In the case of a combination therapy device, the proposed drug deliverydevice provides separate storage containers or cartridge retainers fortwo or more active drug agents. These active drug agents are then onlycombined and/or delivered to the patient during a single deliveryprocedure. These active agents may be administered together in acombined dose or alternatively, these active agents may be combined in asequential manner, one after the other.

The drug delivery device also allows for the opportunity of varying thequantity of the medicaments. For example, one fluid quantity can bevaried by changing the properties of the injection device (e.g., settinga user variable dose or changing the device's “fixed” dose). The secondmedicament quantity can be changed by manufacturing a variety ofsecondary drug containing packages with each variant containing adifferent volume and/or concentration of the second active agent.

The drug delivery device may have a single dispense interface. Thisinterface may be configured for fluid communication with the reservoirin the case of a single medicament device or, in the case of acombination therapy device, a primary reservoir and with a secondaryreservoir of medicament containing at least one drug agent. The drugdispense interface can be a type of outlet that allows the two or moremedicaments to exit the system and be delivered to the patient.

In practical use of medical devices of the above mentioned type, whetherthey be for single or plural medicament delivery, it is necessary toreplace the drug containing reservoir, usually a cartridge, when themedicament(s) is/are exhausted.

A known medicament deliver device is provided with a retainer which ishinged to the device such as to be moved between an open and closedposition. The retainer is configured to hold a medicament reservoir orcartridge. A latch is provided on the device for locking or holding theretainer in the closed position. Access to the retainer for loading orremoving a medicament cartridge is achieved by releasing the latch.Prior to opening the retainer, it is important to ensure the absence ofobstructions that may impede access to the retainer. For example, it isnecessary to retract a piston rod from the medicament cartridge beforemoving the retainer to an open position to avoid damage to the device. Asensor may be provided for sensing whether the retainer door is in anopen or closed position. However, the positioning of the sensor and/orlogic programmed into the device control system in known devices can besuch as to lead to transient states where there are inconsistenciesbetween the actual and sensed state of the device. One example of thismay be where the retainer is sensed as being open or closed but is infact in transit between these states.

Positioning of the sensor in known devices may contribute to transientstate conditions detracting from accurate sensing of the operating stateof the device. For example, placement of the sensor on the door latchhas led to transient state conditions. This arises because the retainerdoor activates the sensor on the latch as the door moves between theopen and closed position.

The invention therefore faces the technical problem of ensuring anaccurate determination of the state of the device and appropriatecontrol logic to reduce risk of damage to the device arising frominconsistencies between the actual and sensed states of the device.

It is an aim of the present invention to alleviate the aforementioneddifficulties. It is a further aim to simplify user operation of themedicament delivery device through the use of control logic. It is alsoan aim of the present invention to avoid unnecessary or inappropriatedevice functions taking place. It is a further aim of the presentinvention to devise a control logic that alleviates risk of error duringoperating sequences associated with replacement of medicamentcartridges.

According to a first aspect of the present invention, there is provideda medicament delivery device for the administration of one or more drugagents, the device having a dispense interface for providing fluidiccommunication between an outlet and a medicament cartridge retainer, aninterface sensor for generating an output indicative of whether thedispense interface is attached to or detached from the device, acontroller for controlling a predetermined operation of the device independence on an output of the interface sensor.

In a preferred embodiment of the first aspect, the dispense interface isconfigured in this device for providing fluid communication from thedevice to an outlet. The outlet may include an attachment for a needlehub. The predetermined operation may relate to a cartridge change orreplacement cycle of the device upon detachment of the interface sensor.In a preferred embodiment, the predetermined operation may be initiationof the cartridge change or replacement cycle.

According to a second aspect of the present invention, there is provideda medicament delivery device for the administration of one or more drugagents, wherein the device comprises a retainer for holding a medicamentcartridge, the retainer being moveable between an open and closedposition, a retainer sensor for sensing whether the retainer is in aclosed or open position and for sensing presence or absence of acartridge in the retainer, and a controller for controlling apredetermined operation of the device in dependence on an output of theretainer sensor.

The retainer sensor of a device embodying the present invention maycomprise a position sensor for generating a position output indicativeof whether the retainer is in an open or closed position, and acartridge sensor for generating a cartridge output indicative of whetherthe retainer is holding a medicament cartridge. In a preferredembodiment, the controller facilitates control of differentpredetermined operation sequences depending on respective combinationsof outputs from the retainer and position sensors. The predeterminedoperation may relate to identification (or not) of a medicamentcartridge in the retainer.

The first and second aspects of the present invention may be utilised ina single or combination therapy device to make up a cartridge change orreplacement cycle which may be programmed into software of the devicecontroller. In a device embodying the first and second aspects, thefirst aspect is concerned with establishing user access to themedicament cartridge to be replaced, through opening of the retainerdoor, and the second aspect is concerned with device functionalityfollowing closure of the retainer door. The cartridge change orreplacement cycle will be discussed further below.

As noted above, the first and second aspects are applicable to singletherapy devices which have a single medicament stored in a singlereservoir or cartridge. However, they are also applicable to combinationtherapy devices that can accommodate more than one drug agent reservoiror cartridge may include a first retainer and a second retainer forholding a medicament reservoirs or cartridges containing two drug agentsthat may be the same as or different from one another. The medicamentreservoirs or cartridges may contain independent (single drug compound)or pre-mixed (co-formulated multiple drug compounds). The dispenseinterface for a device having first and second retainers may be providedwith a bifurcated conduit for providing fluid communication from thefirst and second retainers to a unitary outlet. The needle hub may beremovably attached to the unitary outlet. Each one of the first andsecond retainers may have an associated position sensor and cartridgesensor so that the cartridge change cycle of the device may beimplemented in respect of each retainer separately.

The medicaments may be the same as or different from one another. Thedevice may have a dose setting mechanism for user setting of anappropriate dose of the one or more drug agents. The retainer or eachretainer in the case of a combination therapy device may have a drivetrain associated with it for automatic or manual delivery of the drugagent(s) to the patient. The drive train may include a piston rod fordriving a bung of the medicament cartridge during a prime or doseoperation of the device. The retainer and door may be coupled togetheror formed integrally as a unitary component of the device. The retaineris secured in a closed position by a latch which is movable between alatched and unlatched position under control of the controller. Theretainer and/or door may be spring loaded so that on release of thelatch by the controller, the retainer door opens such as to present themedicament cartridge held therein accessible to the user.

Devices embodying either aspect of the present invention may include acontrol panel with input means, such as buttons or the like, as well asoutput means, such as a digital display or a sound unit or the like. Theinput means may be configured to receive inputs from a user for dosing,priming functions and the like, whereas the output means may beconfigured to indicate information, permissible/disallowed functions,prompts or guidance to the user. The digital display may be configuredto show if a cartridge retainer is open and which medicament reservoir,filled with what type of medicament, has to be inserted into the openedcartridge retainer. Likewise the digital display and the sound unit maybe configured to indicate if a medicament reservoir has not properlybeen inserted into the respective cartridge retainer. The output meansmay further be configured to indicate information concerning the fillinglevel of the medicament reservoirs.

The controller may include an electronic control unit that may compriseat least an evaluation unit, which is configured to receive signals froma sensor unit. In this configuration the sensor unit may be anelectronic or an electromechanical sensor, which is configured to sendsignals to the evaluation unit dependant on the positions of themedicament or cartridge retainers and/or locking conditions of lockingdevices provided to retain the medicament reservoirs or cartridges inthe device. There may also be a sensor unit, which is configured to sendsignals to the evaluation unit dependant on the correct insertion of themedicament reservoirs. There may further be a sensor unit, which isconfigured to send signals to the evaluation unit dependant on thefilling level of the medicament reservoirs. The sensor units and theevaluation unit may also be one component.

When the dispense interface (i.e. cartridge hub) is detached or removedfrom the device, the controller responds to a signal generated by theinterface sensor by initiating the cartridge change cycle. Thiscomprises a step of activating a cartridge door button or buttons (i.e.one for each retainer) which may be provided on the device for openingthe retainer door. When the cartridge door button is pressed by theuser, the drive train rewinds to a ‘home’ end position and stops. Thisrewinding retracts the piston rod from the medicament cartridge held bythe retainer. The piston rod is retracted to a position that is clear ofthe proximal end of the cartridge. The rewinding of the piston rodcontinues so that its travel goes beyond the proximal end to release thelatch. This allows the retainer door to open under the action of thespring loading. A sensor is provided for detecting a retainer door opencondition. The end position, i.e. fully retracted position, is reachedby the piston rod and this is sensed by the controller. In response tothis, the controller advances the drive train by a distance sufficientto move the latch into a position which permits locking of the retainerwhen the retainer door is closed after loading of the medicamentcartridge. In a device embodying the first and second aspects, thissensor may be provided by the retainer sensor.

The operational procedure of devices embodying the second aspect of thepresent invention is invoked when the controller receives a signal fromthe position sensor, which in a preferred embodiment, may perform thefunction of a cartridge door switch. The operational procedure invokeddepends on the output of the cartridge sensor that is received by thecontroller. In the event that the position sensor indicates that theretainer is closed and the cartridge sensor indicates that the retaineris holding a medicament cartridge, the drive train advances the pistonrod towards the bung of the medicament cartridge until the drive trainstalls. On stalling of the drive train, the controller may optionallyimplement a small rewind or ‘back off’ of the piston rod to reducepressure on the medicament cartridge. A prompt is displayed on thedisplay by the controller to advise the user of the operational statusof the device. The prompt may include “Cartridge O.K.” to signify acorrect loading thereof, followed by a prompt to attach the dispenseinterface, such as “Fit Cartridge Hub”. In a combination therapy devicehaving two cartridge retainers, the prompt may provide the user with anoption to select between changing the other cartridge (e.g. “ChangeOther Cartridge”) or attaching the dispense interface. In the event thatthe user proceeds to attach the dispense interface, the controller mayimplement a mandatory priming operation to remove air from the dispenseinterface. In this case a prompt for the user to prime may be displayed.

In the event that the position sensor indicates that the retainer isclosed and the cartridge sensor indicates that the retainer is notholding a medicament cartridge, a prompt (such as “Insert Cartridge”)for the user to insert a medicament cartridge is displayed on thedevice. The display may present indicia to prompt the user to press thedoor open button for the relevant retainer, optionally providing anillustration or representation of a cartridge being inserted into theretainer. In a combination therapy device, the user may be given theoption of removing the medicament cartridge from the other retainer asappropriate.

A need to replace a medicament cartridge, for example when themedicament is used up, may be indicated on the digital display. Thecontroller software may check whether the interface hub is attached tothe device. If it is, then the display presents a prompt for the user toremove the interface hub in order that the cartridge change cycle can bestarted.

According to a further aspect of the present invention, there isprovided a method of controlling a medicament delivery device having adispense interface, comprising: sensing detachment of the dispenseinterface from the device; sensing actuation of a cartridge door buttonin response to the sensed detachment of the dispense interface andretracting a piston rod from a medicament cartridge retainer of thedevice in response thereto; and opening the medicament cartridgeretainer following retraction of the piston rod.

According to a still further aspect of the present invention, there isprovided a method of controlling a medicament delivery devicecomprising: sensing outputs of a cartridge sensor and a medicamentcartridge retainer position sensor; advancing the piston rod towards themedicament cartridge when the output of the cartridge sensor indicatesthe presence of a cartridge and the output of the medicament cartridgeretainer position sensor indicates the retainer is in a closed position;or prompting insertion of a medicament cartridge when the output of thecartridge sensor does not indicate the presence of a cartridge when theposition sensor indicates that the retainer is in the closed position.

According to a yet further aspect of the present invention, there isprovided a method of controlling a medicament delivery device having adispense interface, comprising: sensing detachment of the dispenseinterface from the device; sensing actuation of a cartridge door buttonin response to the sensed detachment of the dispense interface andretracting a piston rod from a medicament cartridge retainer of thedevice in response thereto; opening the medicament cartridge retainerfollowing retraction of the piston rod; sensing outputs of a cartridgesensor and a medicament cartridge retainer position sensor; and eitheradvancing the piston rod towards the medicament cartridge when theoutput of the cartridge sensor indicates the presence of a cartridge andthe output of the medicament cartridge retainer position sensorindicates the retainer is in a closed position, or prompting insertionof a medicament cartridge when the output of the cartridge sensor doesnot indicate the presence of a cartridge when the position sensorindicates that the retainer is in the closed position.

According to a still further aspect of the present invention, there isprovided a computer program, comprising code which when run on aprocessor, is operative to control a medicament delivery device for theadministration of one or more drug agents, and to control the device to:sense outputs of a cartridge sensor and a medicament cartridge retainerposition sensor; advance a piston rod towards the medicament cartridgewhen the output of the cartridge sensor indicates the presence of acartridge and the output of the medicament cartridge retainer positionsensor indicates the retainer is in a closed position; or promptinsertion of a medicament cartridge when the output of the cartridgesensor does not indicate the presence of a cartridge when the positionsensor indicates that the retainer is in the closed position.

According to another aspect of the present invention, there is provideda computer-readable medium encoded with instructions that, when executedon a computer, control a medicament delivery device for theadministration of one or more drug agents by: sensing outputs of acartridge sensor and a medicament cartridge retainer position sensor;advancing the piston rod towards the medicament cartridge when theoutput of the cartridge sensor indicates the presence of a cartridge andthe output of the medicament cartridge retainer position sensorindicates the retainer is in a closed position; or prompting insertionof a medicament cartridge when the output of the cartridge sensor doesnot indicate the presence of a cartridge when the position sensorindicates that the retainer is in the closed position.

In embodiments of either or both aspects of the present invention, theposition sensor may be located in the device in a location that isseparate from the retainer door latch.

Devices embodying one or both aspects of the present invention may guidethe user through the sequence of operational steps of the device. Thishas the benefit of improving user operability by reducing risk ofinappropriate, wrong or unbeneficial user selection of device functions.A further benefit lies in the avoidance of unnecessary motor movementwith a consequential increase in battery life and avoiding wastage ofdispense interfaces (cartridge hubs) or needle hubs.

The medicament delivery device may be an infusion device or an injectiondevice, for example, a hand-held insulin injection pen. The medicamentdelivery devices embodying the present invention may be used either bymedical personnel or by patients themselves. As an example, type-1 andtype-2 diabetes may be treated by patients themselves by injection ofinsulin doses, for example once or several times per day. The first andsecond retainers may be configured to hold medicament reservoirs orcartridges that contain different drug agents from one another, forexample, a fast acting insulin drug agent in one and a long actinginsulin drug agent in the other. The first and second retainers arepreferably sized differently from one another to ensure the user placesthe correct drug agent in the correct retainer. In embodiments of thepresent invention, the controller may be programmed by software toperform the operations of the device and to indentify the predeterminedstates and non-predetermined states of the device.

These as well as other advantages of various aspects of the presentinvention will become apparent to those of ordinary skill in the art byreading the following detailed description, with appropriate referenceto the accompanying drawings.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates a perspective view of a single medicament cartridgedelivery device embodying the present invention with an end cap of thedevice removed;

FIG. 2 illustrates a perspective view of the delivery device of FIG. 1except that it has dual medicament cartridges;

FIG. 3 illustrates a perspective view of the cartridge retainerillustrated in FIG. 2 with one cartridge retainer in an open position;

FIG. 4 illustrates a cross-sectional view of the dispense interface anddose dispenser mounted onto a drug delivery device, such as the deviceillustrated in FIG. 2;

FIG. 5 is a cross-sectional view of the medical device showingmedicament cartridges and a drive train;

FIGS. 6 a to 6 c are cross-sectional views for illustrating attaching ofthe dispense interface to the device;

FIG. 7 is a cross-sectional view of the attaching or detaching of adispense interface from the medical device; and

FIG. 8 is a flow chart illustrating operation of a device embodying thepresent invention.

DETAILED DESCRIPTION

The drug delivery device illustrated in FIG. 1 comprises a main body 14that extends from a proximal end 16 to a distal end 15. At the distalend 15, a removable end cap or cover 18 is provided. This end cap 18 andthe distal end 15 of the main body 14 work together to provide a snapfit or form fit connection so that once the cover 18 is slid onto thedistal end 15 of the main body 14, this frictional fit between the capand the main body outer surface 20 prevents the cover from inadvertentlyfalling off the main body.

The main body 14 contains a micro-processor control unit, anelectro-mechanical drive train, and a single retainer for holding amedicament reservoir or cartridge. When the end cap or cover 18 isremoved from the device 10 (as illustrated in FIG. 1), a dispenseinterface 201 is mounted to the distal end 15 of the main body 14, and adose dispenser (e.g., a needle assembly) is attached to the interface.The dispense interface 201 provides a fluidic communication between theneedle assembly and the medicament reservoir held within the device. Thedrug delivery device 10 can be used to administer a computed dose of amedicament through a single needle assembly.

A control panel region 60 is provided near the proximal end of the mainbody 14. Preferably, this control panel region 60 comprises a digitaldisplay 80 along with a plurality of human interface elements that canbe manipulated by a user to set and inject a combined dose. In thisarrangement, the control panel region comprises a first dose settingbutton 62, a second dose setting button 64 and a third button 66designated with the symbol “OK”. In addition, along the most proximalend of the main body, an injection button 74 is also provided (notvisible in the perspective view of FIG. 1). A cartridge holder 40 can beremovably attached to the main body 14 and may contain a singlecartridge retainer (not shown).

The embodiment shown in FIG. 2, has similar elements to the embodimentof FIG. 1 except that the cartridge holder 40, which can also beremovably attached to the main body 14, may contain at least twocartridge retainers 50 and 52. Each retainer is configured so as tocontain one medicament reservoir, such as a glass cartridge. Preferably,each cartridge contains a different medicament.

In addition, at the distal end of the cartridge holder 40, the drugdelivery device illustrated in FIG. 2 includes a dispense interface 200for providing fluidic communication between the needle assembly and themedicament reservoirs held within the device. In one arrangement, thisdispense interface 200 includes a main outer body 212 that is removablyattached to a distal end 42 of the cartridge holder 40. As for theembodiment of FIG. 1, a distal end 214 of the dispense interface 201 issimilarly provided and preferably comprises a needle hub 216. Thisneedle hub 216 may be configured so as to allow a dose dispenser, suchas a conventional pen type injection needle assembly, to be removablymounted to the drug delivery device 10.

Once the device is turned on, the digital display 80 of the FIG. 1 andFIG. 2 embodiments illuminates and provides the user certain deviceinformation, preferably information relating to the medicament(s)contained within the cartridge holder 40. For example, the user isprovided with certain information relating to the single medicament ofFIG. 1 or both the primary medicament (Drug A) and the secondarymedicament (Drug B) of FIG. 2.

As shown in FIG. 3, first and second cartridge retainers 50, 52 comprisehinged cartridge retainers. These hinged retainers allow user access tothe cartridges. FIG. 3 illustrates a perspective view of the cartridgeholder 40 with the first hinged cartridge retainer 50 in an openposition. FIG. 3 illustrates how a user might access the first cartridge90 by opening up the first retainer 50 and thereby having access to thefirst cartridge 90. The cartridge holder 40 of FIG. 1 is provided with asingle retainer similar to either retainer 50 or 52 of the embodiment ofFIG. 2.

A dose dispenser or needle assembly that may be used with the interface200 is also illustrated and is provided in a protective outer cap (notshown). The dispense interface 200 illustrated in FIG. 4 is showncoupled to the cartridge holder 40. The axial attachment means betweenthe dispense interface 200 and the cartridge holder 40 can be any knownaxial attachment means to those skilled in the art, including snaplocks, snap fits, snap rings, keyed slots, and combinations of suchconnections. The connection or attachment between the dispense interfaceand the cartridge holder may also contain additional features (notshown), such as connectors, stops, splines, ribs, grooves, pips, clipsand the like design features, that ensure that specific hubs areattachable only to matching drug delivery devices. Such additionalfeatures would prevent the insertion of a non-appropriate secondarycartridge to a non-matching injection device.

FIG. 4 also shows a needle assembly 400. This has a double ended needle406 and a hub 401. The double ended needle or cannula 406 is fixedlymounted in a needle hub 401. This needle hub 401 comprises a threaded(not shown) inner wall to allow the needle hub 401 to be screwed ontothe dispense interface 200 which, in one preferred arrangement, isprovided with a corresponding outer thread along a distal hub.Alternative releasable connectors may also be provided such as a snaplock, a snap lock released through threads, a bayonet lock, a form fit,or other similar connection arrangements. The double ended needle 406 ismounted centrally through the needle hub 401 such that a first or distalpiercing end 405 forms an injecting part for piercing an injection site(e.g., the skin of a user). Similarly, a second or proximal piercing end407 protrudes from an opposite side of the assembly 400. This second end407 pierces a septum 270 of the dispense interface 200.

The dispense interface 200 is shown in cross-section in FIG. 4. In thisone preferred arrangement, this interface 200 comprises: a) a main outerbody 210; b) a first inner body 220; c) a second inner body 230; d) afirst piercing needle 240; e) a second piercing needle 250; f) a valveseal 260; and g) the septum 270.

The dispense interface 200 is configured to be removably connected tothe cartridge holder 40 by way protrusions 217 provided on the cartridgeholder 40 and corresponding recesses 218 provided on the dispenseinterface. These co-operate to form an interference fit, form fit, orsnap lock between the dispense interface 200 and the cartridge holder40. Alternatively, and as those of skill in the art will recognize, anyother similar connection train that allows for the dispense interfaceand the cartridge housing 40 to be axially coupled could be used aswell.

The dispense interface 200 and the distal end of the cartridge holder 40act to form an axially engaging snap lock or snap fit arrangement thatcould be axially slid onto the distal end of the cartridge housing. Inone alternative arrangement, the dispense interface 200 may be providedwith a coding feature so as to prevent inadvertent dispense interfacecross use. That is, the inner body of the hub could be geometricallyconfigured so as to prevent an inadvertent cross use of one or moredispense interfaces.

In addition, as can be seen in FIG. 4, a proximal surface 226 near theproximal end of the first inner body 220 may be configured with at leasta first proximally positioned piercing needle 240 comprising a proximalpiercing end portion 244. Similarly, the first inner body 220 isconfigured with a second proximally positioned piercing needle 250comprising a proximally piercing end portion 254. Both the first andsecond needles 240, 250 are rigidly mounted on the proximal surface 226of the first inner body 220.

Preferably, this dispense interface 200 further comprises a valvearrangement. Such a valve arrangement could be constructed so as toprevent cross contamination of the first and second medicamentscontained in the first and second reservoirs, respectively. A preferredvalve arrangement may also be configured so as to prevent back flow andcross contamination of the first and second medicaments.

In one preferred system, dispense interface 200 includes a valvearrangement in the form of a valve seal 260. Such a valve seal 260 maybe provided within a cavity 231 defined by the second inner body 230, soas to form a holding chamber 280. Preferably, cavity 231 resides alongan upper surface of the second inner body 230. This valve seal comprisesan upper surface that defines both a first fluid groove 264 and secondfluid groove 266. For example, FIG. 4 illustrates the position of thevalve seal 260, seated between the first inner body 220 and the secondinner body 230. During an injection step, this seal valve 260 helps toprevent the primary medicament in the first pathway from migrating tothe secondary medicament in the second pathway, while also preventingthe secondary medicament in the second pathway from migrating to theprimary medicament in the first pathway. Preferably, this seal valve 260comprises a first non-return valve 262 and a second non-return valve268. As such, the first non-return valve 262 prevents fluid transferringalong the first fluid pathway 264, for example a groove in the sealvalve 260, from returning back into this pathway 264. Similarly, thesecond non-return valve 268 prevents fluid transferring along the secondfluid pathway 266 from returning back into this pathway 266.

Together, the first and second grooves 264, 266 converge towards thenon-return valves 262 and 268 respectively, to then provide for anoutput fluid path or a holding chamber 280. This holding chamber 280 isdefined by an inner chamber defined by a distal end of the second innerbody both the first and the second non return valves 262, 268 along withthe pierceable septum 270. As illustrated, this pierceable septum 270 ispositioned between a distal end portion of the second inner body 230 andan inner surface defined by the needle hub of the main outer body 210.

The holding chamber 280 terminates at an outlet port of the interface200. This outlet port 290 is preferably centrally located in the needlehub of the interface 200 and assists in maintaining the pierceable seal270 in a stationary position. As such, when a double ended needleassembly is attached to the needle hub of the interface (such as thedouble ended needle 406), the output fluid path allows both medicamentsto be in fluid communication with the attached needle assembly.

Axially sliding the main outer body 210 over the distal end of the drugdelivery device attaches the dispense interface 200 to the multi-usedevice. In this manner, a fluid communication may be created between thefirst needle 240 and the second needle 250 with the primary medicamentof the first cartridge and the secondary medicament of the secondcartridge, respectively. FIG. 4 illustrates the dispense interface 200mounted onto the distal end 42 of the cartridge holder 40. The cartridgeholder 40 is illustrated as having a first cartridge 90 containing afirst medicament 92 and a second cartridge 100 containing a secondmedicament 102.

When the interface 200 is first mounted over the distal end of thecartridge holder 40, the proximal piercing end 244 of the first piercingneedle 240 pierces the septum of the first cartridge 90 and therebyresides in fluid communication with the primary medicament 92 of thefirst cartridge 90. A distal end of the first piercing needle 240 willalso be in fluid communication with a first fluid path groove 264defined by the valve seal 260.

Similarly, the proximal piercing end 254 of the second piercing needle250 pierces the septum of the second cartridge 100 and thereby residesin fluid communication with the secondary medicament 102 of the secondcartridge 100. A distal end of this second piercing needle 250 will alsobe in fluid communication with a second fluid path groove 266 defined bythe valve seal 260.

It will be apparent that when the medical device 10 is brought into usefor the first time there will be air in the first and second fluidconduits 264, 266 and the holding chamber 280 of the dispense interface200 as well as the cannula 406 of the needle hub 400. Consequently, itis desirable to prime the device 10 by ejecting medicament through theconduits until medicament appears at the distal end of the needle hub400; thereby ensuring that air has been expelled from the fluidcommunication channels between the cartridges 90, 100 and the end of thecannula 406 to be inserted into a patient. Furthermore, in the event ofreplacement of one or both of the cartridges 90, 100, it may be afunctional requirement programmed into the device that the dispenseinterface 400 be removed before either one of the retainers 50, 52 canbe unlocked. In this case, the device 10 will require priming afterreplacement of the cartridge and replacement of the dispense interface200 or a new dispense interface 200. The volume of the conduits withinthe dispense interface 200 to be filled during priming may be in theorder of 1 μl.

FIG. 5 illustrates the medical device 10 in cross-sectional view. Thetwo cartridge retainers 50 and 52 are illustrated in the closedposition. Retainer 50 is configured so as to contain medicamentreservoir 620, whereas retainer 52 is configured so as to containmedicament reservoir 622. The reservoirs 620, 622 may be glass, metal orplastic cartridges. Reservoir 622 may have a smaller diameter and ashorter length than reservoir 620. The cartridge holder 40 may furthercomprise two locking devices 600 and 602. The locking devices 600 and602 may be designed as latches, which may lock the cartridge retainers50, 52 in a form-fitting manner in their closed position. The lockingdevices 600 and 602 may be released or unlocked by operation of retainerdoor or cartridge release buttons 504 and 506. The retainer door orcartridge release buttons 504 and 506 may work mechanically orelectromechanically.

The cartridge holder 40 further contains two cartridge retainer springs608 and 610, which in the closed position of the cartridge retainers 50and 52 exert an elastic spring force on the cartridge retainers. Byreleasing the locking devices 600 and 602 the spring force causes thecartridge retainers 50 and 52 to move in the open position. Cartridgeretainer 50 is hinged to the cartridge retainer housing at pivot bearing612, whereas cartridge retainer 52 is hinged to the cartridge retainerhousing at pivot bearing 614. The cartridge retainers 50, 52 are therebypivotable about the pivot bearings 612, 614 between their closed andtheir open position.

Retainer sensors for each of the retainers 50 and 52 may be provided andconfigured to detect the insertion condition of the respectivemedicament cartridges 620, 622 and/or the closing condition of thecartridge retainers 50 and 52. In the embodiment of FIG. 5, the retainersensors which are provided in the cartridge holder 40 are shown tocomprise position sensors 613 and 615 for sensing whether the retainers50 and 52 respectively are in a closed or open position. Separatecartridge sensors or detect switches 616 and 618 are provided forsensing the presence or absence of a cartridge in the retainers 50 and52 respectively. The position sensors 613, 615 are located in the devicein a location that is separate from the retainer door latches 600, 602.

The device 10 further comprises a controller 700, which may be amicro-processor control unit. The controller 700 receives signals fromthe position sensors 613, 615 and cartridge sensors 616, 618.

An output from the cartridge sensor 616 for the cartridge 620 mayindicate that the cartridge is correctly located within the device. Thiscondition is most likely to occur when the cartridge retainer 50 of thedevice is closed with the cartridge 620 inserted. When either thecartridge retainer 50 is closed and the cartridge 620 is absent or thecartridge retainer 50 is open the controller 700 should detect that thecartridge is absent. The position switch 613 indicates that thecartridge retainer 50 is either open or closed, regardless of thepresence or absence of a cartridge.

The conditions indicated in table 1 below can be achieved with acombination of the respective cartridge sensors 616, 618 and therespective position sensors 613, 615. For the purposes of describing theintended behaviour of the system, a ‘1’ in the cartridge sensor columnindicates that a cartridge has been detected and a ‘1’ in the positionsensor indicates that the door is closed. A ‘0’ in either of thesecolumns has the opposite sense to a ‘1’.

The table 1 below shows possible combinations of cartridge and retainersensors.

TABLE 1 Cartridge and Cartridge retainer sensor states CartridgeRetainer Typical condition when the sensor combination Condition SensorSensor occurs A 0 0 The retainer is open with the cartridge eitherinserted in the retainer or removed from the retainer. These areconditions expected during a cartridge change event. B 0 1 The retaineris closed but there is either an incorrect cartridge or no cartridgelocated in the door. This is the condition expected when the doors havebeen shut without a cartridge loaded, during storage for example. C 1 0The retainer is open and the device has detected the presence of acartridge. This is an ERROR condition and will be reported on the userinterface. D 1 1 The retainer is closed and a cartridge has beendetected. This is the condition expected for dose delivery.

The outputs from these sensors may be subject to transitional states,for example, if the cartridge retainer 50 is closed with a cartridge inplace, either the position sensor 613 or the cartridge sensor 615 maytrigger first. The transitional states may be due to, for example,tolerances. So, depending on which sensor switch triggers first, thecontroller 700 may determine states: “cartridge retainer closed—nocartridge”; or the “cartridge retainer open—cartridge present”, thelatter being an illogical state.

The configuration and behaviour of the sensors for cartridge 622 isessentially the same as for cartridge 620 described above.

The device 10 further comprises a memory unit, for example a read-onlymemory unit being connected to controller 700, which may have programmedtherein software to be executed by the controller 700 for performing thefunctions of the device, as will be described in more detail withreference to FIGS. 7 and 8 below. The controller 700 may comprise anevaluation unit 702, which may be configured to receive signals from theposition sensors 613 and 615 as well as from the cartridge detectswitches 616 and 618. The evaluation unit 702 may also be configured toreceive signals from sensors that are configured to determine thefilling level of the cartridges 620, 622.

The controller 700 is further connected to a user interface, for examplethe control panel region 60. Preferably, the control panel region 60comprises output means such as the digital display 80 and input meanssuch as dose setting buttons 62 and 64 or the button 66 designated withthe symbol “OK” (shown in a different position in the embodiment ofFIGS. 1-3 from the embodiment of FIG. 7). At the proximal end of themain body 14, an injection button 74 is provided.

FIG. 5 also shows a pair of drive trains 624 and 625. The first drivetrain 624 of the pair includes a motor 626 that drives a piston rod 627via a gear 628. The drive train 624 is operative to drive the piston rod627 under the control of the controller 700 to dispense medicament fromthe cartridge 620. A second drive train 625 includes a motor 629 fordriving a piston rod 630 via a second gear mechanism 631, to dispensemedicament from the cartridge 622 also under the control of thecontroller 700.

FIGS. 6 a to 6 c are schematic cross-sectional views of the dispenseinterface 200 showing an interface sensor 600. This may comprise a pushrod 601. For instance, the interface sensor 600 is at least partiallyarranged in a cavity formed by the cartridge holder 40 such as cavity 43in FIG. 4.

At the proximal end of the push rod 601, a spring 602 is arranged whichis connected to the cartridge holder 40 such that the push rod 601 isresiliently hold in the drug delivery device 10 and is at leastlongitudinally movable in the drug delivery device.

The detecting arrangement 600 may further comprise a first switch 603and a second switch 604 which are longitudinally arranged at a side-wallof the cavity 43. Therein, the first switch 603 is arranged closer tothe distal end 42 of the cartridge holder 40 than the second switch. Inother words, the first switch 603 is distally positioned and the secondswitch 604 is proximally positioned in the drug delivery device 10. Thefirst switch 603 and the second switch 604 are pressure activatedswitches forming a first and a second detecting unit. In particular, thefirst switch 603 and the second switch 604 are only activated, whenpressure is applied on the respective switch, and otherwise deactivated.The switches may be connected to a micro-processor control unit of thedrug delivery device 10, for instance (logically signalling activationand deactivation to the micro-processor control unit).

A lateral surface of the push rod 601 oriented towards the first switch603 and the second switch 604 is formed from three portions, twoparallel surface portions 605, 606 and an inclined surface portion 607.The inclined surface portion 607 is arranged between the parallelsurface portions 605, 606 such that the parallel surface portion 605 atthe proximal end of the push rod is set back. A rod 608 is arranged atthe distal end of the push rod 601.

In FIG. 6 a the dispense interface 200 is not attached to the drugdelivery device 10. In particular, there is no contact between the rod608 and the surface 226 of the dispense interface 200. Accordingly, thespring 602 is relaxed and the push rod 601 is hold in a first positionin the drug delivery device 10. In this first position of the push rod601 in the drug delivery device 10, the first switch 603 and the secondswitch 604 face the set back parallel surface portion 605 and the spring602, respectively. In particular, there is no contact between thelateral surface of the push rod 601 and the first switch 603 and thesecond switch 604. Both switches are deactivated.

In FIG. 6 b, attachment of the dispense interface 200 to the drugdelivery device 10 is initiated, the dispense interface 200 is alignedto the distal end 42 of the cartridge holder 40 and pushed towards thedrug delivery device 10 to axially slide over the distal end 42 of thecartridge housing 40 of the drug delivery device 10. Thereby, the distalend of the rod 608 resides on the surface 226 of the dispense interface200 and is also pushed towards the drug delivery device 10 such that,during attaching the dispense interface 200 to the drug delivery device10, the movement of the dispense interface 200 towards the drug deliverydevice facilitates a corresponding movement of the push rod 601 and acompression of the spring 602.

When the push rod 601 is correspondingly moved, the first switch 603 andthe second switch 604 slide along the inclined surface portion 607 ofthe lateral surface of the push rod 601 towards the parallel surfaceportion 606 and, thereby, increasing pressure is applied on theswitches. When a pressure threshold is overcome, the first switch 603and the second switch 604 are activated, for instance, the switches areactivated, when residing on the parallel surface portion 606 (i.e. anactivating portion of the push rod). Due to its distal position, thefirst switch 603 resides on the parallel surface portion 606 before thesecond switch 604 resides thereon and is, thus, earlier activated. Whenthe attaching is initiated as illustrated in FIG. 6 b, the first switch603 resides on the parallel surface portion 606 and is activated.

In FIG. 6 c, attaching of the dispense interface 200 to the drugdelivery device 10 is completed such that the septae of the firstcartridge 90 and the second cartridge 100 are pierced and the dispenseinterface resides in fluid communication with the primary medicament 92of the first cartridge 90 and the secondary medicament 102 of the secondcartridge 100 as described above.

When the attaching of the dispense interface 200 to the drug deliverydevice 10 is completed as illustrated in FIG. 6 c, the second switch 604also resides on the parallel surface portion 606 and is activated. Thespring 602 is compressed and the push rod is in a second position.

When the dispense interface 200 is released from the drug deliverydevice 10, the compressed spring 602 relaxes and moves the push rod 601back to the first position and optionally the dispense interface 200 toa detent position (i.e. the position illustrated in FIG. 6 b). Thereby,firstly the second switch 604 and then the first switch 603 slide alongthe inclined surface portion 607 towards the set back parallel surface605 and are subsequently deactivated. This enables the controller 700 tosense detachment of the dispense interface 200.

Although FIGS. 6 a to 6 c show two switches 603, 604, embodiments mayemploy a single switch for the interface sensor 600.

The operation of devices embodying the present invention will bedescribed with reference to FIGS. 7 and 8.

FIG. 7 illustrates the process of exchanging a cartridge in a medicaldelivery device 10. In step 800 the controller 700 of the medical device10 determines that the cartridge in retainer 50 is empty, or the userchooses to replace the cartridge, and so the controller 700 goes into a‘cartridge exchange or replacement mode’. For example, the device mayinhibit the setting of a dose that is greater than the medicamentremaining in the cartridge. Accordingly, the digital display 80indicates that drug B (medicament cartridge 620) is empty. Likewise instep 800 the digital display 80 illustrates the cartridge 620 which hasa big diameter and a great length as being the one that needsexchanging.

Before the user is allowed access to the cartridge holder 50, the deviceinstructs the user to remove the dispense interface at step 802. Thiscorresponds to step 900 of FIG. 8 and is indicated on the digitaldisplay 80. The indications on the digital display 80 shown in steps 800and 802 may alternate during a certain period. Subsequently, thedispense interface 200 is removed from the cartridge holder 40 in step802 by the user.

In step 804 the controller 700 determines the dispense interface 200being removed from the cartridge holder 40 by sensing signals from theswitch or switches 603 and 604, as indicated by step 905 in FIG. 8.Further in step 804 the controller 700 may operate the locking devices600 and 602 into an unlockable condition, in case they have been in anot-unlockable condition while the dispense interface 200 has beenattached to the cartridge holder 40. At the same time the controller 700activates the retainer door or cartridge release button 504 (step 910)corresponding to the cartridge to be exchanged, that is, cartridge 620.The controller 700 displays a prompt on the digital display 80 for theuser to operate the cartridge release button 504. When the user pressesthe cartridge release button 604, this is sensed at step 915 whereuponthe controller 700 causes the drive train 624 to retract the piston rod627 (step 920) from the cartridge 620, displaying a “Please wait”instruction (shown as a rotating hour glass in 806 of FIG. 7) on thedisplay as the piston rod 627 is retracted from the cartridge 620. Whenthe piston rod 627 is fully retracted, the motor 626 stalls and a signalis sent to the controller 700 to trigger the locking device 600 into anunlocked or released condition thus allowing the opening of thecartridge retainer 50 (step 925 “Open Door). In the event that there isno cartridge in the retainer, the drive train may rewind by a smalldistance sufficient to release the latch. At the time of the motorstall, an encoder (not shown) for monitoring the drive train is put intoa “datum reset” condition by the controller 700. Also, at this time, thelocking device 602 is operated into a non-unlockable condition, in casethis has not been conducted before so that only one cartridge retainer50, 52 can be opened at a time.

In step 808 the cartridge retainer 50 is pushed out of the closedposition into the open position by the cartridge retainer spring 608. Itis also possible that cartridge retainer 50 is pulled out into the openposition by the user, without the aid of elastic spring forces. As soonas the cartridge retainer 50 has been opened, the detection switch 616sends an according signal to the controller 700. The digital display 80subsequently indicates to insert a new cartridge 622, filled with drugB, and illustrates a cartridge which has a big diameter and a greatlength (step 930). At step 930, the user may load a new cartridge, closethe retainer door leaving the retainer empty or even reinsert theexisting cartridge.

Opening of the cartridge retainer 50 is sensed by the controller 700whereupon the motor 626 is run for sufficient time to advance the pistonrod 627 by a distance that will permit resetting of the locking device600 when it is closed by the user after cartridge replacement. Thedetection switch 616 associated with the retainer 50 is provided todetect the presence of the cartridge 620 in the retainer 50 when closed.In the subsequent step 810 the cartridge retainer 50 is manually movedinto the closed position (step 940), where it is locked by the lockingdevice 600. When the retainer 50 is closed, the controller 700 senses asignal from the position sensor 613 provided to detect closure of theretainer 50. If the retainer 50 is not fully closed, no signal from theposition sensor 613 will be sensed by the controller (step 945) and sothe controller will provide an indication on the display 80 to close theretainer door (step 950). When in the closed position, this is sensed bythe controller 700 (step 945). The controller 700 requires sensing of anoutput from the detection switch 616 to confirm the presence of acartridge in the retainer 50 at step 955. If a replacement cartridge isdetected by the detection switch 616, a corresponding signal is sensedby the controller 700 at step 955. If a cartridge is not sensed at step955, a prompt is displayed at step 960 for the user to press theretainer door button, which in turn is detected at step 915. The promptmay additionally or instead correspond to the prompt illustrated at 804of FIG. 7.

After successful placement of a new cartridge 620 in the retainer 50 andsuccessful closure of the retainer 50, the detection switch 616 signalsto the controller 700 that a cartridge is present and the positionsensor 613 sends a signal to the controller that the door is closed. Thesuccessful insertion condition of the inserted cartridge may furthermorebe indicated on the digital display 80 (see step 810 of FIG. 7),whereupon the controller advances the piston rod to the bung of thereplacement cartridge at step 970. The cartridge exchange processdescribed above may be applicable to the other cartridge 622 and itsreplacement into cartridge retainer 52 according to a routine of stepsthat corresponds to steps 800 to 810 (and steps 900 to 990 of FIG. 8)described above. If the device is operative to detect that the othercartridge is also empty or requires changing, then at step 975 this willbe indicated on the display 80 as in step 800, but indicating Drug Ainstead of Drug B. The controller will activate the retainer door button506 corresponding to this cartridge whereupon pressing of this buttonmay be detected at step 915. If the device does not indicate change ofthe other cartridge, the user may still access it by pressing theretainer door button 506. If the other cartridge is not to be replaced,the controller 700 causes display of a prompt for the display interfaceto be fitted at step 980. Fitting of the dispense interface is detectedwhereupon the controller may display at step 990 a prompt for the userto implement a priming operation.

The steps 800 to 810 (and steps 900 to 990) described with reference toFIGS. 7 and 8 are applicable to the device of FIG. 1 having a singlecartridge retainer.

The operational sequences of FIG. 7 or 8 may be performed by a computerprogram that may be stored on a computer-readable medium such as aCD-ROM 992 or a memory stick 993.

The term “drug” or “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exedin-3 or exedin-4 or an analogue or derivative ofexedin-3 or exedin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyhepta

decanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequence HHis-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2, H-(Lys)5-des Pro36,des Pro37 Exendin-4(1-39)-NH2, des Pro36 [Asp28] Exendin-4(1-39), desPro36 [IsoAsp28] Exendin-4(1-39), des Pro36 [Met(O)14, Asp28]Exendin-4(1-39), des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39), desPro36 [Trp(O2)25, Asp28] Exendin-4(1-39), des Pro36 [Trp(O2)25,IsoAsp28] Exendin-4(1-39), des Pro36 [Met(O)14 Trp(O2)25, Asp28]Exendin-4(1-39), des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28]Exendin-4(1-39); or des Pro36 [Asp28] Exendin-4(1-39), des Pro36[IsoAsp28] Exendin-4(1-39), des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39), des Pro36 [Trp(O2)25,Asp28] Exendin-4(1-39), des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39), des Pro36[Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;or an Exendin-4 derivative of the sequence

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2, des Asp28 Pro36,Pro37, Pro38Exendin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro38 [Asp28]Exendin-4(1-39)-NH2, H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28]Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38 [Asp28]Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28]Exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28]Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36 [Trp(O2)25, Asp28]Exendin-4(1-39)-Lys6-NH2, H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25]Exendin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25,Asp28] Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25,Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36[Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2, des Met(O)14 Asp28 Pro36,Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14,Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5 des Pro36, Pro37, Pro38[Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-Lys6-des Pro36[Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2, H-des Asp28Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25] Exendin-4(1-39)-NH2,H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25,Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28] Exendin-4(S1-39)-(Lys)6-NH2,H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exedin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150 kDa) that are also knownas immunoglobulins which share a basic structure. As they have sugarchains added to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, θ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and δ approximately 500 amino acids, whileμ and ε have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (CH) and the variable region (VH). In onespecies, the constant region is essentially identical in all antibodiesof the same isotype, but differs in antibodies of different isotypes.Heavy chains γ, α and δ have a constant region composed of three tandemIg domains, and a hinge region for added flexibility; heavy chains μ andε have a constant region composed of four immunoglobulin domains. Thevariable region of the heavy chain differs in antibodies produced bydifferent B cells, but is the same for all antibodies produced by asingle B cell or B cell clone. The variable region of each heavy chainis approximately 110 amino acids long and is composed of a single Igdomain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H—H interchaindisulfide bond. F(ab′)2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1 C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

1-12. (canceled)
 13. A medicament delivery device for the administrationof one or more drug agents, wherein the device comprises a retainer forholding a medicament cartridge, the retainer being moveable between anopen and closed position, a position sensor for generating a positionoutput indicative of whether the retainer is in an open or closedposition, a cartridge sensor for generating a cartridge outputindicative of whether the retainer is holding a medicament cartridge,and a controller for controlling a predetermined operation of the devicein dependence on an output of the position sensor and on an output ofthe cartridge sensor, further comprising a dispense interface forproviding fluidic communication between an outlet and a medicamentcartridge retainer, an interface sensor for generating an outputindicative of whether the dispense interface is attached to or detachedfrom the device, the controller being operative for controlling apredetermined operation of the device in dependence on an output of theinterface sensor and wherein the predetermined operation relates to acartridge change cycle of the device upon detachment of the dispenseinterface.
 14. A medicament delivery device according to claim 13,wherein the controller facilitates control of different predeterminedoperational sequences depending on the outputs from the cartridge andposition sensors.
 15. A medicament delivery device according to claim14, wherein a first predetermined operational sequence is implemented bythe controller when the cartridge sensor indicates that the retainer isholding a medicament cartridge and the position sensor indicates thatthe retainer is in a closed position, and the device includes a drivetrain for advancing or retracting a piston rod to or from the retainer,and the first one of said predetermined operational sequences includesadvancing the piston rod to the medicament cartridge.
 16. A medicamentdelivery device according to claim 14, wherein a second predeterminedoperational sequence is implemented by the controller when the cartridgesensor indicates that the retainer is not holding a medicament cartridgeand the position sensor indicates that the retainer is in a closedposition, and wherein the second predetermined operational sequenceincludes displaying a prompt to insert a cartridge in the device.
 17. Amedicament delivery device according to claim 13 comprising a latch forholding the retainer in a closed position, the controller beingoperative to release the latch and allow opening of the retainer independence on detection of the dispense interface.
 18. A medicamentdelivery device according to claim 17, wherein the predeterminedoperation is an initiation of the cartridge change cycle.
 19. Amedicament delivery device according to claim 18, wherein the deviceincludes a cartridge retainer door button and initiation of thecartridge change cycle comprises detecting that the cartridge retainerdoor button is activated.
 20. A medicament delivery device according toclaim 19, wherein the device includes a piston rod and drive train, thecontroller being operative to retract the piston rod from the medicamentcartridge on activation of the cartridge door button.
 21. A medicamentdelivery device according to claim 13, wherein the device is hand-held.22. A medicament delivery device according to claim 21, wherein thedevice is a pen-type injection device.
 23. A medicament delivery deviceaccording to claim 13 comprising first and second retainers each forholding a medicament cartridge.
 24. A method of controlling a medicamentdelivery device having a dispense interface, comprising: sensingdetachment of the dispense interface from the device; sensing actuationof a cartridge door button in response to the sensed detachment of thedispense interface and retracting a piston rod from a medicamentcartridge retainer of the device in response thereto; opening themedicament cartridge retainer following retraction of the piston rod;sensing outputs of a cartridge sensor and a medicament cartridgeretainer position sensor; and either advancing the piston rod towardsthe medicament cartridge when the output of the cartridge sensorindicates the presence of a cartridge and the output of the medicamentcartridge retainer position sensor indicates the retainer is in a closedposition, or prompting insertion of a medicament cartridge when theoutput of the cartridge sensor does not indicate the presence of acartridge when the position sensor indicates that the retainer is in theclosed position.